scholarly journals Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits

Science ◽  
2021 ◽  
Vol 371 (6530) ◽  
pp. eabd9704 ◽  
Author(s):  
Bradley M. Colquitt ◽  
Devin P. Merullo ◽  
Genevieve Konopka ◽  
Todd F. Roberts ◽  
Michael S. Brainard
Keyword(s):  
Neural Circuits ◽  
Expression Patterns ◽  
Regulatory Gene ◽  
Vocal Learning ◽  
Aminobutyric Acid ◽  
Projection Neurons ◽  
Complex Behavior ◽  
Developmental Origins ◽  
Motor Pathway ◽  
Single Cell Rna Sequencing

Birds display advanced behaviors, including vocal learning and problem-solving, yet lack a layered neocortex, a structure associated with complex behavior in mammals. To determine whether these behavioral similarities result from shared or distinct neural circuits, we used single-cell RNA sequencing to characterize the neuronal repertoire of the songbird song motor pathway. Glutamatergic vocal neurons had considerable transcriptional similarity to neocortical projection neurons; however, they displayed regulatory gene expression patterns more closely related to neurons in the ventral pallium. Moreover, while γ-aminobutyric acid–releasing neurons in this pathway appeared homologous to those in mammals and other amniotes, the most abundant avian class is largely absent in the neocortex. These data suggest that songbird vocal circuits and the mammalian neocortex have distinct developmental origins yet contain transcriptionally similar neurons.

scholarly journals Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Vocal Learning ◽  
Brain Regions ◽  
Motor Deficits ◽  
Mrna Levels ◽  
Adult Males ◽  
Protein Levels ◽  
Area X

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

scholarly journals Cryopreservation of microglia enables single-cell RNA sequencing with minimal effects on disease-related gene expression patterns

iScience ◽  
2021 ◽  
Vol 24 (4) ◽  
pp. 102357
Author(s):  
Brenda Morsey ◽  
Meng Niu ◽  
Shetty Ravi Dyavar ◽  
Courtney V. Fletcher ◽  
Benjamin G. Lamberty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Related Gene ◽  
Single Cell Rna Sequencing ◽  
Disease Related Gene

scholarly journals Sox9 expression in canine epithelial skin tumors

2015 ◽  
Vol 59 (3) ◽  
Author(s):  
E. Fantinato ◽  
L. Milani ◽  
G. Sironi
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Hair Follicle ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Regulatory Gene ◽  
Skin Neoplasms ◽  
Stem Cell Marker ◽  
Molecular Characteristics

<p><em>Sox9</em> is a master regulatory gene involved in developmental processes, stem cells maintenance and tumorigenesis. This gene is expressed in healthy skin but even in several skin neoplasms, where its expression patterns often resembles those of the developing hair follicle. In this study, samples from eleven different types of canine skin neoplasms (squamous papilloma, squamous cell carcinoma, infundibular keratinizing acanthoma, inferior tricholemmoma, isthmic tricholemmoma, trichoblastoma, trichoepitelioma, malignant trichoepitelioma, pilomatricoma, subungual keratoacanthoma, subungual squamous cell carcinoma) were immunohistochemically stained and evaluated for <em>Sox9</em> with the aim to correlate tumor phenotype with molecular characteristics that may help to better define tumor development, contribute to its diagnosis and clinical management. Keratoacanthoma excluded, all the skin neoplasms examined showed a variable positivity to <em>Sox9</em>, especially in the basal layers, but with major intensity in neoplasms developing from the bulge region of the hair follicle, as trichoblastoma. According to our results, <em>Sox9</em> could be employed as a stem cell marker to better assess the role of stem cells in canine epidermal and follicular tumors.</p>

scholarly journals Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

2020 ◽  
Author(s):  
Ziheng Zhou ◽  
Shuguang Wang ◽  
Dengwei Zhang ◽  
Xiaosen Jiang ◽  
Jie Li ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Single Cell ◽  
Developmental Trajectories ◽  
Expression Patterns ◽  
Development Stage ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Cerebral Cortex Development ◽  
Excitatory Neurons ◽  
Human And Mouse

AbstractBackgroundThe specification and differentiation of neocortical projection neurons is a complex process under precise molecular regulation; however, little is known about the similarities and differences in cerebral cortex development between human and mouse at single-cell resolution.ResultsHere, using single-cell RNA-seq (scRNA-seq) data we explore the divergence and conservation of human and mouse cerebral cortex development using 18,446 and 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types and their markers genes. By single-cell trajectories analysis we find human and mouse excitatory neurons have different developmental trajectories of neocortical projection neurons, ligand-receptor interactions and gene expression patterns. Further analysis reveals a refinement of neuron differentiation that occurred in human but not in mouse, suggesting that excitatory neurons in human undergo refined transcriptional states in later development stage. By contrast, for glial cells and inhibitory neurons we detected conserved developmental trajectories in human and mouse.ConclusionsTaken together, our study integrates scRNA-seq data of cerebral cortex development in human and mouse, and uncovers distinct developing models in neocortical projection neurons. The earlier activation of cognition -related genes in human may explain the differences in behavior, learning or memory abilities between the two species.

scholarly journals With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding

2021 ◽  
Vol 14 ◽  
Author(s):  
Carlos Sánchez-Huertas ◽  
Eloísa Herrera
Keyword(s):  
Growth Cone ◽  
Intracellular Signaling ◽  
Expression Patterns ◽  
Brain Regions ◽  
Extracellular Proteins ◽  
Projection Neurons ◽  
Axon Pathfinding ◽  
Guidance Receptors ◽  
Spatio Temporal ◽  
Intracellular Cascades

During the establishment of neural circuitry axons often need to cover long distances to reach remote targets. The stereotyped navigation of these axons defines the connectivity between brain regions and cellular subtypes. This chemotrophic guidance process mostly relies on the spatio-temporal expression patterns of extracellular proteins and the selective expression of their receptors in projection neurons. Axon guidance is stimulated by guidance proteins and implemented by neuronal traction forces at the growth cones, which engage local cytoskeleton regulators and cell adhesion proteins. Different layers of guidance signaling regulation, such as the cleavage and processing of receptors, the expression of co-receptors and a wide variety of intracellular cascades downstream of receptors activation, have been progressively unveiled. Also, in the last decades, the regulation of microtubule (MT) assembly, stability and interactions with the submembranous actin network in the growth cone have emerged as crucial effector mechanisms in axon pathfinding. In this review, we will delve into the intracellular signaling cascades downstream of guidance receptors that converge on the MT cytoskeleton of the growing axon. In particular, we will focus on the microtubule-associated proteins (MAPs) network responsible of MT dynamics in the axon and growth cone. Complementarily, we will discuss new evidences that connect defects in MT scaffold proteins, MAPs or MT-based motors and axon misrouting during brain development.

Afferent influences on cell death and birth during development of a cortical nucleus necessary for learned vocal behavior in zebra finches

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 13-24
Author(s):  
F. Johnson ◽  
S. W. Bottjer
Keyword(s):  
Vocal Learning ◽  
Afferent Input ◽  
Vocal Behavior ◽  
Projection Neurons ◽  
Zebra Finches ◽  
Vocal Development ◽  
Neuron Death ◽  
Cortical Nucleus ◽  
Alternate Source ◽  
Cortical Regions

Forebrain nuclei that control learned vocal behavior in zebra finches are anatomically distinct and interconnected by a simple pattern of axonal pathways. In the present study, we examined afferent regulation of neuronal survival during development of the robust nucleus of the archistriatum (RA). RA projection neurons form the descending motor pathway of cortical vocal-control regions and are believed to be directly involved in vocal production. RA receives afferent inputs from two other cortical regions, the lateral magnocellular nucleus of the anterior neostriatum (lMAN) and the higher vocal center (HVC). However, because the ingrowth of HVC afferent input is delayed, lMAN projection neurons provide the majority of afferent input to RA during early vocal learning. lMAN afferent input to RA is of particular interest because lMAN is necessary for vocal learning only during a restricted period of development. By making lesions of lMAN in male zebra finches at various stages of vocal development (20-60 days of age) and in adults (&gt;90-days old), we asked whether the survival of RA neurons depends on lMAN afferent input, and if so whether such dependence changes over the course of vocal learning. The results showed that removal of lMAN afferent input induced the loss of over 40% of RA neurons among birds in early stages of vocal development (20 days of age). However, lMAN lesions lost the ability to induce RA neuron death among birds in later stages of vocal development (40 days of age and older). These findings indicate that many RA neurons require lMAN afferent input for their survival during early vocal learning, whereas the inability of lMAN lesions to induce RA neuron death in older birds may indicate a reduced requirement for afferent input or perhaps the delayed ingrowth of HVC afferent input (at approx. 35 days of age) provides an alternate source of afferent support. Removal of lMAN afferent input also dramatically increased the incidence of mitotic figures in RA, but only among 20-day-old birds at 2 days post-lesion. The early, acute nature of the mitotic events raises the possibility that cell division in RA may be regulated by lMAN afferent input.

scholarly journals Single-Cell RNA Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells

Circulation ◽  
2020 ◽  
Vol 142 (19) ◽  
pp. 1848-1862 ◽  
Author(s):  
David T. Paik ◽  
Lei Tian ◽  
Ian M. Williams ◽  
Siyeon Rhee ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Receptor Expression ◽  
Transcriptional Networks ◽  
Sequencing Data ◽  
Tissue Specific ◽  
Functional Relationships ◽  
Single Cell Rna Sequencing

Background: Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably imprinted in the transcriptome, the pathways and networks that sustain EC heterogeneity have not been fully delineated. Methods: To investigate the transcriptomic basis of EC specificity, we analyzed single-cell RNA sequencing data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We used a number of bioinformatics tools to uncover markers and sources of EC heterogeneity from single-cell RNA sequencing data. Results: We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either single-cell RNA sequencing or bulk RNA sequencing, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (eg, liver, brain), whereas others (ie, adipose, heart) have considerable transcriptomic overlap with ECs from other tissues. We identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. Sex was a considerable source of heterogeneity in the endothelial transcriptome and we discovered Lars2 to be a gene that is highly enriched in ECs from male mice. We found that markers of heart and lung ECs in mice were conserved in human fetal heart and lung ECs. We identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns. Conclusions: We used single-cell RNA sequencing data generated by the Tabula Muris consortium to uncover transcriptional networks that maintain tissue-specific EC identity and to identify novel angiocrine and functional relationships between tissue-specific ECs.

scholarly journals Interneuron Diversity: Toward a Better Understanding of Interneuron Development In the Olfactory System

2019 ◽  
Vol 13 ◽  
pp. 117906951982605
Author(s):  
Chi-Jen Yang ◽  
Kuo-Ting Tsai ◽  
Nan-Fu Liou ◽  
Ya-Hui Chou
Keyword(s):  
Olfactory System ◽  
Neural Circuits ◽  
Projection Neurons ◽  
Intrinsic Properties ◽  
Recent Advances ◽  
Local Interneurons ◽  
Olfactory Interneurons ◽  
High Diversity ◽  
Interneuron Development

The Drosophila olfactory system is an attractive model for exploring the wiring logic of complex neural circuits. Remarkably, olfactory local interneurons exhibit high diversity and variability in their morphologies and intrinsic properties. Although olfactory sensory and projection neurons have been extensively studied of development and wiring; the development, mechanisms for establishing diversity, and integration of olfactory local interneurons into the developing circuit remain largely undescribed. In this review, we discuss some challenges and recent advances in the study of Drosophila olfactory interneurons.

scholarly journals Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tobias Weinberger ◽  
Dena Esfandyari ◽  
Denise Messerer ◽  
Gulce Percin ◽  
Christian Schleifer ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Immune Cells ◽  
Transcriptional Response ◽  
Developmental Origins ◽  
Adult Mice ◽  
Single Cell Rna Sequencing ◽  
Mapping Analysis ◽  
Health And Disease ◽  
Arterial Inflammation ◽  
Cellular Identity

Abstract Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.

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